Long-term changes in the dentoalveolar system of rats after experimental intra-abdominal hypertension

Aim. To establish the effect of experimental intra-abdominal hypertension (IAH) on the teeth-jaw system of rats in the long-term period based on the study of pro-inflammatory cytokines and morphological analysis of the elements of the temporomandibular joint (TMJ) and salivary glands.

Materials and methods. The experiment was carried out on 60 newborn rats; IAH was modelled by injecting collagen into the abdominal cavity to a predetermined level of intra-abdominal pressure. The rats were evenly (n = 20) divided into 3 groups: 1st - control; 2nd and 3rd - with light and severe IAH, respectively. Serum levels of IL-18, MCP-1, NGAL were determined by multiplex analysis after 10 and 120 days, VEGF-C - after 10 days - by ELISA. The morphological examination of the TMJ and salivary glands was performed using a Leica DM2000 microscope after 120 days.

Results. After 10 days and 120 days, blood serum levels of NGAL, IL-18 and MCP-1 were statistically significantly increased in groups 2 and 3 compared to the control; the concentration of MCP-1 increased in proportion to the severity of the IAH with the maximum values in group 3. After 10 days, the level of VEGF was significantly increased in group 2 compared to the control group (p < 0.02). Inflammation of the TMJ was observed significantly more often in groups 2 and 3 than in the control group (p = 0.0002). In group 3, circulatory disorders and bone marrow degeneration of the TMJ, as well as inflammation, circulatory disorders and hyperplasia of the lymphoid tissue of the salivary glands were statistically significantly more often compared to groups 1 and 2.

Conclusion. In the long term, experimental IAH showed an increase in the levels of markers of inflammation and hypoxia in the blood serum of rats; the severity of synovitis and sialadenitis grew with an increase in the level of intra-abdominal pressure; the maximum deviations in inflammation markers and morphological changes in the TMJ and salivary glands of rats were observed in the group with severe IAH.

1. Liang Y.J., Huang H.M., Yang H.L., et al. Controlled peritoneal drainage improves survival in children with abdominal compartment syndrome. Ital J Pediatr. 2015; 41: 29. https://doi.org/10.1186/s13052-015-0134-6. PMID: 25881886

2. Kirkpatrick A.W., Roberts D.J., Jaeschke R., et al. Methodological background and strategy for the 2012-2013 updated consensus definitions and clinical practice guidelines from the abdominal compartment society. Anaesthesiol Intensive Ther. 2015; 47 Spec No: s63-77. https://doi.org/10.5603/AIT.a2015.0081. PMID: 26588481

3. Divarci E., KarapinarB., YalazM., et al. Incidence and prognosis of intraabdominal hypertension and abdominal compartment syndrome in children. J Pediatr Surg. 2016; 51(3): 503-507. https://doi.org/10.1016/jjpedsurg.2014.03.014. PMID: 25783342

4. Elverdin J.C., Chiarenza A.P., Frid A.B., Giglio M.J. Effects of chronic hypoxia on the secretory responses of rat salivary glands. Arch Oral Biol. 1995; 40(5): 459-462. https://doi.org/10.1016/0003-9969(94)00158-8. PMID: 7543749

5. Яковлев В.В., Бадаева А.В., ИвановаЕ.И. и др. VEGF-C - биомаркер повреждения почек при экспериментальной интрааб-доминальной гипертензии. Сеченовский вестник. 2020; 11(3): 47-56. https://doi.org/10.47093/2218-7332.2020.11.3.47-56

6. De Laet I.E., Malbrain M.L.N.G., De Waele J.J. A Clinician’s Guide to Management of Intra-abdominal Hypertension and Abdominal Compartment Syndrome in Critically Ill Patients. Crit Care. 2020 Mar 24; 24(1): 97. https://doi.org/10.1186/s13054-020-2782-1. PMID: 32204721

7. Morozov D., Morozova O., Pervouchine D., et al. Hypoxic renal injury in newborns with abdominal compartment syndrome (clinical and experimental study). Pediatr Res. 2018 Feb; 83(2): 520-526. https://doi.org/10.1038/pr.2017.263. Epub 2017 Nov 15. PMID: 29053704

8. Aqrawi L.A., Chen X., Hynne H., et al. Cytokines Explored in Saliva and Tears from Radiated Cancer Patients Correlate with Clinical Manifestations, Influencing Important Immunoregulatory Cellular Pathways. Cells. 2020 Sep 8; 9(9): 2050. https://doi.org/10.3390/cells9092050. PMID: 32911805

9. Hussain Q.A., McKay I.J., Gonzales-Marin C.,AllakerR.P. Regulation of adrenomedullin and nitric oxide production by periodontal bacteria. J Periodontal Res. 2015 Oct; 50(5): 650-657. https://doi.org/10.1111/jre.12246. Epub 2014 Nov 29. PMID: 25440112

10. Belstr0m D., Eiberg J.M., Enevold C., et al. Salivary microbiota and inflammation-related proteins in patients with psoriasis. Oral Dis. 2020 Apr; 26(3): 677-687. https://doi.org/10.1111/odi.13277. Epub 2020 Jan 28. PMID: 31916654

11. Aqrawi L.A., Galtung H.K., Guerreiro E.M., et al. Proteomic and histopathological characterisation of sicca subjects and primary Sjogren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers. Arthritis Res Ther. 2019 Jul 31; 21(1): 181. https://doi.org/10.1186/s13075-019-1961-4. PMID: 31366407

12. Zhou S., Cui Z., Urban J.P. Factors influencing the oxygen concentration gradient from the synovial surface of articular cartilage to the cartilage-bone interface: a modeling study. Arthritis Rheum. 2004; 50(12): 3915-3924. https://doi.org/10.1002/art.20675. PMID: 15593204

13. Hasegawa S., Nakano T., Torisu K., et al. Vascular endothelial growth factor-C ameliorates renal interstitial fibrosis through lymphangiogenesis in mouse unilateral ureteral obstruction. Lab Invest. 2017; 97(12): 1439-1452. https://doi.org/10.1038/labinvest.2017.77. PMID: 29083411

14. Terrizzi A.R., Conti M.I., Martinez M.P., Fernandez-Solari J. The process of acclimation to chronic hypoxia leads to submandibular gland and periodontal alterations: an insight on the role of inflammatory mediators. Mediators Inflamm. 2018; 2018: 6794508. https://doi.org/10.1155/2018/6794508. PMID: 30622434